Dansyl-Labeled Cholic Acid as a Tool To Build Speciation Diagrams for the Aggregation of Bile Acids

2012 ◽  
Vol 116 (51) ◽  
pp. 14776-14780 ◽  
Author(s):  
Miguel Gomez-Mendoza ◽  
M. Luisa Marin ◽  
Miguel A. Miranda
Keyword(s):  
Bile Acids ◽  
Cholic Acid ◽  
Speciation Diagrams

Adaptive responses of renal organic anion transporter 3 (OAT3) during cholestasis

2008 ◽  
Vol 295 (1) ◽  
pp. F247-F252 ◽  
Author(s):  
Jiarong Chen ◽  
Tomohiro Terada ◽  
Ken Ogasawara ◽  
Toshiya Katsura ◽  
Ken-ichi Inui
Keyword(s):  
Bile Acids ◽  
Cholic Acid ◽  
Molecular Mechanisms ◽  
Competitive Inhibition ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Specific Substrate ◽  
Renal Secretion ◽  
Sd Rats ◽  
Anion Transporter

During cholestasis, bile acids are mainly excreted into the urine, but adaptive renal responses to cholestasis, especially molecular mechanisms for renal secretion of bile acids, have not been well understood. Organic anion transporters (OAT1 and OAT3) are responsible for membrane transport of anionic compounds at the renal basolateral membranes. In the present study, we investigated the pathophysiological roles of OAT1 and OAT3 in terms of renal handling of bile acids. The Eisai hyperbilirubinemic rats (EHBR), mutant rats without multidrug resistance-associated protein 2, showed higher serum and urinary concentrations of bile acids, compared with Sprague-Dawley (SD) rats (wild type). The protein expression level of rat OAT3 was significantly increased in EHBR compared with SD rats, whereas the expression of rat OAT1 was unchanged. The transport activities of rat and human OAT3, but not OAT1, were markedly inhibited by various bile acids such as chenodeoxycholic acid and cholic acid. Cholic acid, glycocholic acid, and taurocholic acid, which mainly increased during cholestasis, are transported by OAT3. The plasma concentration of β-lactam antibiotic cefotiam, a specific substrate for OAT3, was more increased in EHBR than in SD rats despite upregulation of OAT3 protein. This may be due to the competitive inhibition of cefotiam transport by bile acids via OAT3. In conclusion, the present study clearly demonstrated that OAT3 is responsible for renal secretion of bile acids during cholestasis and that the pharmacokinetic profile of OAT3 substrates may be affected by cholestasis.

scholarly journals Medical treatment of gallstones

1978 ◽  
Vol 16 (18) ◽  
pp. 69-71
Keyword(s):  
Medical Treatment ◽  
Bile Acids ◽  
Cholic Acid ◽  
Chenodeoxycholic Acid ◽  
The Other ◽  
Naturally Occurring ◽  
Made In

Chenodeoxycholic acid (CDCA) (Chendol - Weddel) is one of two naturally occurring ‘primary’ bile acids (the other being cholic acid) made in the liver from cholesterol. CDCA is synthesised commercially from cholic acid and prescribed as gelatin-coated capsules containing 125 mg CDCA.

Radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid from human serum, with use of 125I-labeled ligands.

1979 ◽  
Vol 25 (2) ◽  
pp. 264-268 ◽  
Author(s):  
O Mäentausta ◽  
O Jänne
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Chenodeoxycholic Acid ◽  
Deoxycholic Acid ◽  
Serum Samples ◽  
Analytical Recovery ◽  
Hepatobiliary Diseases ◽  
Polyethylene Glycol Precipitation ◽  
Free Serum

Abstract We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). Before radioimmunoassay, 0.1-mL serum samples were precipitated with nine volumes of ethanol, and portions from the supernate were used in the assays. The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates. 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 3.2 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +/- SD) of the bile acid conjugates in serum from apparently healthy women and men (in mumol/L) were: cholic acid conjugates, 0.43 +/- 0.17 (n = 126); chenodeoxycholic acid conjugates, 0.47 +/- 0.23 (n = 111); and deoxycholic acid conjugates, 0.33 +/- 0.11 (n = 96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases.

Interaction between bile acids and staphylococcal polysaccharide: inhibition of capsule formation in encapsulated mutant strains (taurine+, taurine−) of Staphylococcus aureus

1983 ◽  
Vol 29 (12) ◽  
pp. 1653-1660 ◽  
Author(s):  
Toshichika Ohtomo
Keyword(s):  
Staphylococcus Aureus ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Taurocholic Acid ◽  
Polysaccharide Antigen ◽  
Capsule Formation ◽  
Mutant Strains ◽  
Bile Acid Derivatives ◽  
Capsular Material

In a previous paper, we showed that bile acid derivatives inhibit capsule formation as well as taurine biosynthesis in a taurine+ (Tau+) encapsulated strain of Staphylococcus aureus. In the present study, binding of [14C]cholic acid ([14C]CA) and [14C]taurocholic acid ([14C]TA) to the staphylococcal polysaccharide antigen (SPA) of the capsular fraction was examined. The bile acids were found to bind with SPA via taurine of the Tau+ cells. [14C]CA bound with the SPA fraction of the Tau+ strain within 10–30 min, whereas 60–120 min was required in the binding of [14C]TA. Various bile acids competed with cholic acid binding to Tau+ cells which was shown by the inhibition of binding with cholic acid or taurocholic acid but not with glycholic acid. Binding of bile acid derivatives to a Tau− encapsulated mutant or to capsular material from this mutant was not observed.

scholarly journals Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria

2018 ◽  
Vol 84 (10) ◽  
Author(s):  
Heidi Doden ◽  
Lina A. Sallam ◽  
Saravanan Devendran ◽  
Lindsey Ly ◽  
Greta Doden ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Deoxycholic Acid ◽  
Gut Bacteria ◽  
Dietary Lipids ◽  
Human Gut ◽  
Content Type ◽  
Low Activity

ABSTRACTBile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacteriumClostridium leptum; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such asClostridium scindens,Clostridium hylemonae, andClostridium hiranonis. Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread amongFirmicutes,Actinobacteriain theCoriobacteriaceaefamily, and human gutArchaea.IMPORTANCE12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteriaC. scindens,C. hiranonis, andC. hylemonae. Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract.

scholarly journals Microbiological degradation of bile acids. The preparation of some hypothetical metabolites involved in cholic acid degradation

1976 ◽  
Vol 154 (3) ◽  
pp. 577-587 ◽  
Author(s):  
S Hayakawa ◽  
Y Kanematsu ◽  
T Fujiwara ◽  
H Kako
Keyword(s):  
Fatty Acid ◽  
Carboxylic Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Valeric Acid ◽  
Side Chain ◽  
Partial Synthesis ◽  
Arthrobacter Simplex ◽  
Acid Degradation ◽  
Oxidation Mechanisms

1. To identify the intermediates involved in the degradation of cholic acid, the further degradation of (4R)-4-[4a-(2-carboxyethyl)-3aa-hexahydro-7ab-methyl-5-oxoindan-1β-yl]valeric acid (IVa) by Arthrobacter simplex was attempted. The organism could not utilize this acid but some hypothetical intermediate metabolities of compound (IVa) were prepared for later use as reference compounds. 2. The nor homologue (IIIa) and the dinor homologue (IIIb) of compound (IVa) were prepared by exposure of 3-oxo-24-nor-5β-cholan-23-oic acid (I) and (20S)-3b-hydroxy-5-pregnene-20-carboxylic acid (II) to A. simplex respectively. These compounds correspond to the respective metabolites produced by the shortening of the valeric acid side chain of compound (IVa) in a manner analogous to the conventional fatty acid a- and b-oxidation mechanisms. Their structures were confirmed by partial synthesis. 3. The following authentic samples of reduction products of the oxodicarboxylic acids (IIIa), (IIIb) and (IVa) were also synthesized as hypothetical metabolities: (4R)-4-[3aa-hexahydro-5a-hydroxy-4a-(3-hydroxypropyl)-7ab-methylindan-1b-yl]valeric acid (Vb) and its nor homologue (VIIa) and dinor homologue (IXa);(4R)-4-[3Aaa-hexahydro-5a-hydroxy-4a-(3-hydroxypropyl)-7ab-methylindan-1b-yl]-pentan-1-ol (Vc); and their respective 5β epimers (Ve), (VIIc), (IXc) and (Vf). 4. In connexion with the non-utilization of compound (IVa) by A. simplex, the possibility that not all the metabolites formed from cholic acid by a certain micro-organism can be utilized by the same organism is considered.

scholarly journals Studies on the origin of biliary phospholipid. Effect of dehydrocholic acid and cholic acid infusions on hepatic and biliary phospholipids

1990 ◽  
Vol 270 (3) ◽  
pp. 691-695 ◽  
Author(s):  
F Chanussot ◽  
H Lafont ◽  
J Hauton ◽  
B Tuchweber ◽  
I Yousef
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Bile Flow ◽  
Normal Values ◽  
Specific Radioactivity ◽  
Regulatory Effect ◽  
Experimental Protocol ◽  
Dehydrocholic Acid ◽  
Cellular Organelles

The correlation between the secretion of biliary phospholipid (PL) and bile acid suggests a regulatory effect of bile acid on PL secretion. Bile acids may influence PL synthesis and/or the mobilization of a preformed PL pool. The objective of this study was to determine the contribution of these two sources to biliary PL, by using an experimental protocol in which dehydrocholic acid (DHCA) and cholic acid (CA) were infused to manipulate biliary PL secretion. In control rats, there was a steady state in bile flow. PL secretion and the biliary secretion of newly synthesized phosphatidylcholine (PC). The specific radioactivity of PC in bile was significantly higher than in plasma, microsomes and canalicular membranes. DHCA infusion decreased biliary PC secretion rate by 80%, and secretion returned to normal values at the transport maximum of CA. The specific radioactivity of biliary PC was decreased by 30% by DHCA infusion and reached normal values during CA infusion. There were no significant changes in the specific radioactivity of PC in plasma or cellular organelles during infusion of bile acids. These data indicate that: (1) newly synthesized PC contributes a small percentage to biliary PC; thus a preformed pool (microsomal and extrahepatic) is a major source of biliary PL; (2) the contribution of the extrahepatic pool to the biliary PL may be more important than the microsomal pool.

Bile acids. LII. The synthesis of 24-nor-5α-cholic acid and its 3β-isomer

Steroids ◽  
1976 ◽  
Vol 28 (5) ◽  
pp. 655-667 ◽  
Author(s):  
Yehuda Shalon ◽  
William H. Elliott
Keyword(s):  
Bile Acids ◽  
Cholic Acid

scholarly journals Bile salts of the green turtle Chelonia mydas (L.)

1978 ◽  
Vol 171 (2) ◽  
pp. 409-412 ◽  
Author(s):  
G A D Haslewood ◽  
S Ikawa ◽  
L Tökés ◽  
D Wong
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Green Turtle ◽  
Bile Salts ◽  
Deoxycholic Acid ◽  
Enterohepatic Circulation ◽  
Chelonia Mydas ◽  
Independent Evolution ◽  
Alpha 7

1. Bile salts of the green turtle Chelonia mydas (L.) were analysed as completely as possible. 2. They consist of taurine conjugates of 3 alpha, 7 alpha, 12 alpha, 22 xi-tetrahydroxy-5 beta-cholestan-26-oic acid (tetrahydroxysterocholanic acid) and 3 alpha 12 alpha, 22 xi-trihydroxy-5 beta-cholestan-26-oic acid, with minor amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5beta-cholan-24-oic acid (cholic acid), 3alpha, 12 alpha-dihydroxy-5beta-cholan-24-oic acid (deoxycholic acid) and possibly other bile acids. 3. Cholic acid and deoxycholic acid represent the first known examples of bile acids common to chelonians and other animal forms: they may indicate independent evolution in chelonians to C24 bile acids. 4. The discovery of a 7-deoxy C27 bile acid is the first evidence that C27 bile acids or their conjugates have an enterohepatic circulation.

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